Chemotherapy, Immunosuppressive, and Hematology Drugs Flashcards
Alkylating Agents: Nitrogen Mustards
MOA
- causes abnormal base pairing, misreading of the genetic code, and excision of bases = prevents DNA replication and RNA transcription = cell death
But also toxic to most rapidly growing normal cells –> bone marrow, GI epithelial cells, hair
Why see ADR = vomiting, diarrhea, ulcers, alopecia
Cyclophosphamide (Procytox)
Alkylating Agent
For carcinomas, sarcomas, feline lymphoproliferative diseases, mammary carcinoma and lymphoma
It’s a prodrug = hepatic metabolism forms active metabolites = hydroxyphosphamide and aldophosphamide
ADR
- dose-dependent bone marrow toxicity = leukopenia, neutropenia, thrombocytopenia
- GI: vomiting, diarrhea
- Hemorrhagic cystitis (look likes a UTI but it’s sterile)
- Alopecia
Chlorambucil -> Leukeran
Alkylating Agent
Similar to cyclophosphamide but less potent and less toxic
Expensive
Immunosuppressive drug of choice for cats after prednisone
Nitrosoureas: The ‘mustine/CNU’ drugs
Also alkylate the DNA
Lipid-soluble -> very good oral bioavailability
- since enters cells passively = no efflux pump resistance
For lymphomas, mast cell tumors, anecdotally for brain tumors
Leukopenia and can cause thrombocytopenia
Streptozocin -> Zanosar
Nitrosoureas
Used for insulinomas
- mainly in referring practice
ADR
- can cause tubular necrosis -> so only use with IV fluid diuresis
- can result in Type I diabetes
- vomiting common in dogs
Cisplatin: Platinol
Platinum-based drugs
MOA
- inhibits DNA synthesis
Used for solid tumours = osteosarcomas, carcinomas, mast cell tumours
Nephrotoxicity is limiting factor to therapy
Vomiting and Diarrhea
DON’T USE IN CATS
- can cause rapidly fatal pulmonary edema
Carboplatin
Platinum-based drug
less nephrotoxic than cisplatin
Thrombocytopenia
Can be used in cats
Anti-metabolites -> Cellular enzyme inhibitors
Drugs that mess up metabolism w/in the cell
Toceranib -> Palladia
Enzyme inhibitor -> tyrosine kinase
- tx of cutaneous mast cell tumors
Anti-tumour and anti-angiogenic activity
Vincristine -> Oncovin
Vinca alkaloids
- derived from periwinkle plant
Used in lymphoma protocols
ADR
- tissue necrosis if given perivascular (make 100% sure that catheter is in the vein)
Constipation
Therapy for immune-mediated thrombocytopenia
Doxorubicin -> Adriamycin
Anthracine (anti-tumour) antibiotics
Red death
Also for lymphosarcoma, osteosarcoma, mammary carcinomas and other tumours
ADR - if given perivascular = severe tissue necrosis - cardiotoxicity - acute bone marrow suppression Less sever ADR - alopecia - GI toxicity - hypersensitivity rxn from mast cell degranulation
Glucocorticoids
Chemotherapy
Stimulates appetite and attitude
Decreases cachexia from TNS
Glucocorticoids (Immune-mediating)
Very generalized immunosuppression
The anti-inflammatory or immunosuppressive effects are dose-dependent
Alters leukocyte migration and function
- decreases function of monocytes, macrophages, and lymphocytes
- cell-mediated immunity is decreased most
Prednisone or prednisolone
Dexamethasone
Isuflupredone (Predef 2X)
Start parenteral and then continue PO
- rule of thumb w/ steroids for immunosuppression => start w/ injections to get more of an immediate effect and then have owners continue PO at home
- start aggressive then taper
Azathioprine (Imuran)
Immunosuppresive
Purine anti-metabolite = interferes w/ DNA synthesis
Oral or injectable
Metabolized in liver to an active and inactive metabolite
- lots of variability bw animals
Variety of immunosuppressive uses in dogs
- lymphocytes more susceptible
Side Effects
- Myelosuppression
- especially in cats due to decreased hepatic clearance
- anemia
- Pancreatitis and increased liver enzymes
- rebound hyper-immune response if rapid discontinuation
Chlorambucil (Leukeran)
Alkylating agent that cross-links DNA
Similar to cyclophosphamide but less potent/toxic
Use for lymphocytic/plasmacytic infiltrative diseases => IBD, indolent ulcers, pemphigus, atopy
Side Effects
- myelosuppression and vomiting
Expensive to used for cats and small dogs
Cyclosporine (Atopica)
Inhibits cytoplasmic enzyme calceurin phsophatase => decreased IL-2 prod
- decreased cytokines = decreased T-cell activation, chemotaxis, antigen presenting cells, mast cell and eosinophil infiltration
Capsules for dogs
Solution for cats
- control of feline allergic dermatitis
- Eosinophilic granuloma/indolent ulcer
- Plasmacytic stomatitis
F highly variable
Topical ophthalmic -> Optimmune
- keratoconjunctivitis sicca/KCS
- chronic superficial keratitis/CSK in dogs
Adverse Effects
- In general pretty safe and effects we see are mild and rare
- vomiting
- Gingival hyperplasia
- Drug interactions => P-gp/CYP substrates
2nd line systemic immunosuppressants
Sometimes used as adjuncts in IMHA dogs
Leflunomide (Arava)
Mycophenolate Mofetil
Apoquel (oclacitinib)
Derm-specific immunosuppressive
Stops production of certain cytokines (IL-31)
For control of pruritus associated w/ allergic dermatitis
And control of atopic dermatitis in dogs at least 1 yr
Adverse Effects (rare)
- Immunosuppression => secondary infection, demodecosis
- Low incidence of V/D
Cytopoint (lokivetMAB)
Derm-specific immunosuppressive
Same target compound as Apoquel (i.e. IL-31) just different method
- canine monoclonal antibody against IL-31
Aids in reduction of clinical signs associated w/ atopic dermatitis in dogs
- reduces pruritus
- DOESN’T SOLVE UNDERLYING ALLERGY PROBLEM
SC injection and has long duration of effect (>30d)
Can be used concurrently w/ other AD therapy
Erythropoietin/EPO/Epoetin
Hematologic drug –> RBC stimulation
Used in anemia due to CKD -> bc EPO produced in kidney peritubular cells
- Myelodysplasia (not enough RBC production)
Antithrombic Drugs
Prevent thrombosis but not so much to cause hemorrhage
Includes anticoagulants, thrombolytics, antiplatelet drugs
Heparin
Anticoagulant
It’s a GAG that’s negatively charged
Has significant anticoagulant activities
Dicoumarol
Warfarin
Anticoagulants
Interfere w/ Vit K-dependent coagulation factors
Thrombolytics
Enhance clot breakdown/fibrinolysis by stim conversion of plasminogen to plasmin
Includes streptokinase and tPA
